Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in NC/Nga mice

Pharm Res. 2005 Oct;22(10):1627-33. doi: 10.1007/s11095-005-6834-7. Epub 2005 Sep 26.

Abstract

Purpose: CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and the suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to a tape-stripped skin of NC/Nga mouse, a human atopic dermatitis (AD) model, by evaluating the production of cytokines and immunoglobulin isotypes.

Methods: Model antigen, ovalbumin (OVA), and CpG-ODN were applied on to the shaved skin. The penetration of OVA and CpG-ODN was evaluated using confocal laser scanning microscopy (CLSM). Secretion of cytokine from splenocytes and changes in immunoglobulin isotype levels were determined by enzyme-linked immunosorbent assay (ELISA).

Results: Through CLSM it was revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Coadministration of CpG-ODN and OVA to the skin elicited an antigen-specific, Th1-predominant immune response and enhanced the production of IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. In terms of antigen-specific antibody production, the level of IgG2a regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed.

Conclusions: Administration of CpG-ODN with antigen through the skin may shift the immune response from a Th2- to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases such as AD, which is characterized by Th2-dominated inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Topical
  • Animals
  • Antibodies / blood
  • Antigens / administration & dosage
  • Antigens / immunology*
  • Cytokines / metabolism
  • Dermatitis, Atopic / drug therapy
  • Dermatitis, Atopic / immunology*
  • Disease Models, Animal
  • Male
  • Mice
  • Oligodeoxyribonucleotides / administration & dosage*
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Skin / drug effects
  • Skin / immunology*
  • Skin Tests
  • Spleen / chemistry
  • Spleen / metabolism
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Antigens
  • CPG-oligonucleotide
  • Cytokines
  • Oligodeoxyribonucleotides
  • Ovalbumin